Controlled-release dispensers that operate on a diffusional mechanism are well known. In general, there are two basic types of such devices: one in which the agent to be dispensed is dispersed in an agent-permeable polymeric matrix; and the other in which the active agent is contained within a reservoir bounded wholly or partly by an active agent-permeable polymeric membrane. In both types of devices the agent dissolves in the polymer and diffuses through it to the surface of the dispenser and thence to the environment of use. Dispensers of this type have been used for dispensing a variety of active agents to environments of use, such as administration of drugs to animals, including humans, administration of agricultural chemicals to crops or pests, administration of chemicals to water for sanitation purposes, administration of fragrances to mask obnoxious odors, and administration of catalysts to chemical reactions. In general these prior dispensers have been temperature-insensitive except to the extent that the solubility of the agent in the polymer or the coefficient of diffusion varied with temperature. In the polymers used previously in diffusional-type dispensers this variation typically has not been significant.
The present invention uses a type of polymer called a side-chain crystallizable polymer as the diffusional barrier in diffusional-type active agent dispensers. These polymers exhibit permeability to molecules of interest that varies significantly as a function of temperature. These temperature-dependent permeation properties permit applicant to make temperature-sensitive dispensers which can be turned on and off by temperature variation or whose rate of release can be increased significantly by a temperature increase.
Several prior art references have involved the use of side-chain crystallizable polymers as elements in active agent dispensers. U.S. Pat. No. 3,608,549 describes a capsule for administering drugs. The wall of the capsule is made of a drug-permeable nonmelting elastomer such as silicone rubber. The core of the capsule consists of a meltable polymer matrix which contains the drug and a metal coil. The meltable matrix is described as a material which has a solid, crystalline state at low temperature in which it has a low coefficient of diffusion to the drug and a liquid state at higher temperatures in which it has a high coefficient of diffusion to the drug. The metal coil is heated by induction to cause the meltable matrix to become liquid and thus permeable to the drug. Once this occurs, the drug diffuses from the device at a rate controlled by its rate of diffusion through the nonmelting capsule wall. The patent lists several materials that melt at 40.degree.-47.degree. C., including one, poly(stearyl acrylate), that is a side-chain crystallizable polymer. The use of a meltable polymer in this patented device is, however, different in several respects from the use of side-chain crystallizable polymers in the present invention. In the present invention the side-chain crystallizable polymer is in the form of a body that retains its shape and does not become wholly liquid. Also, the side-chain crystallizable polymer is the primary release-rate controlling element in the present invention. Further, in most embodiments of the invention dispenser the side-chain crystallizable polymer is not an internal element of the dispenser but instead defines a surface that interfaces with the environment of use.
U.S. Pat. No. 4,558,690 describes an anticancer capsule comprising an anti-neoplastic agent encapsulated in a meltable polymer. Polyoctadecyl acrylate, a side-chain crystallizable polymer, is used as the meltable polymer. Once the composition has been delivered to the tumor, nonionizing radiation is used to locally heat the tumor and melt the capsule wall so that it disintegrates and permits the agent to be released by dissolution. In such a capsule, the polymer does not retain its shape and drug release does not occur via diffusion through the polymer. U.S. Pat. No. 3,242,051 mentions polyvinyl stearate, another side-chain crystallizable polymer, as a precoating material in a two-step microencapsulation process.
Macromol. Chem. Rapid. Commun. (1986) 7: 33-36 describes the permeation of alkanes through membranes composed of a C.sub.16 methacrylate polymer (a side chain crystallizable polymer) dispersed in a polycarbonate or coated on a porous polysulfone as a function of temperature. Significant increases in alkane permeability were observed at the melting point of the C.sub.16 methacrylate polymer with the membrane composed of the C.sub.16 methacrylate polymer coated on a porous polysulfone support. This reference does not relate to temperature-controlled devices for dispensing active agents.
Crosslinked side-chain crystallizable polymers are described in J. Polymer Sci.: Macromolecular Reviews (1974) 8: 117 and J. Polymer Sci.: Polymer Chemistry Edition (1981) 19: 1871-1873. Applicant knows of no use of crosslinked side-chain crystallizable polymers as diffusion matrices.